Among its many functions, TGF-beta1 up- and down-regulates proliferation of HIV infected cells. We have recently completed a determination of the three dimensional structure of TGF-beta1 in solution. The overall structure is similar to the independently determined X-ray structure of TGF-beta1. However, there are significant differences in the local structures of the two proteins, involving residues 69-74 and hydrophobic sidechains of residues in the ranges 24-33 and 88-102. We are currently analyzing the X-ray and NMR data with the goal of deriving a structure based explanation for the differences in the function of the two TGF-beta isoforms. The significance of this project arises from the unique, detailed structural information that we are deriving about TGF-beta1 in solution. This information will contribute improved understanding of the structure/function relationships of the family of TGF-beta proteins.